12/11/2019 Malignant Melanoma Guidelines: Guidelines Summary, Clinical Presentation and Workup, Surgical Management

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Drugs & Diseases > Oncology

Malignant Melanoma Guidelines

Updated: Feb 17, 2019

Author: Winston W Tan, MD, FACP; Chief Editor: Dirk M Elston, MD more...

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12/11/2019 Malignant Melanoma Guidelines: Guidelines Summary, Clinical Presentation and Workup, Surgical Management

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Sections
Malignant Melanoma

Sections Malignant Melanoma

Overview
Practice Essentials
Background
Etiology
Epidemiology
Prognosis
Patient Education
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Presentation
History
Physical Examination
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DDx
Workup
Approach Considerations
Histologic Findings
Complete Chemistry Panel
Lactate Dehydrogenase Assay
Chest Radiography
MRI
CT Scanning
Positron Emission Tomography
Biopsy of a Suggestive Lesion
Surgical Excision or Reexcision After Biopsy
Elective Lymph Node Dissection
Sentinel Lymph Node Biopsy
Staging
Show All
Treatment
Approach Considerations
Regional Lymph Node Dissection
Adjuvant Therapy
Treatment of Advanced-Stage Melanoma (Stage IV)
Prevention of Malignant Melanoma
Consultations
Long-Term Monitoring
Show All
Guidelines
Guidelines Summary
Clinical Presentation and Workup
Surgical Management
Sentinel Lymph Node Dissection
Mohs Surgery
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12/11/2019 Malignant Melanoma Guidelines: Guidelines Summary, Clinical Presentation and Workup, Surgical Management

Wide Excision Surgical Margins

Radiation Therapy
Treatment for Advanced Melanoma
Follow-up for Melanoma Cancer Survivors
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Medication
Medication Summary
Antineoplastic Agents
Biological Response Modulators
Oncolytic Immunotherapy
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Questions & Answers
Media Gallery
References

Guidelines

Guidelines Summary
Guidelines contributors: Wesley Wu, MD, Resident Physician, Department of Dermatology, Baylor College of
Medicine; Mohsin R Mir, MD, Director, High Risk Skin Cancer Clinic, Assistant Professor, Mohs Surgery, Laser and
Cosmetic Surgery, Department of Dermatology, Baylor College of Medicine

Screening
In 2016, the U.S. Preventive Services Task Force (USPSTF) concluded there is not enough evidence to recommend
for or against routine screening (total body examination by a primary care physician or patient self-examination) for
early detection of skin cancers in the adult general population. [85]

The USPSTF did note the following clinical considerations:

Skin cancer of any type occurs more commonly in men than in women and among persons with a fair
complexion, persons who use indoor tanning beds, and persons with a history of sunburns or previous skin
cancer.
Specific risk factors for melanoma include having an atypical mole, multiple (ie, ≥100) moles, and having a
family history of melanoma.
The risk of melanoma increases with age; the median age at diagnosis is 63 years, and the median age at death is
69 years.
Clinical visual skin examination should assess skin lesions for asymmetry, border irregularity, color variability,
diameter greater than 6 mm or evolution over time (ABCDE criteria)

Next: Clinical Presentation and Workup

Clinical Presentation and Workup

Guidelines from the American Academy of Dermatology (AAD), established in 2011 and updated in 2019, are as
follows [86, 87] :

Skin biopsy remains the first step to establish a definitive diagnosis of cutaneous melanoma.

Preferred biopsy technique is a narrow excisional/complete biopsy with 1- to 3-mm margins that encompass the
entire breadth of lesion and is of sufficient depth to prevent transection at the base. Diagnostic excisional biopsy
can be accomplished by (1) elliptical (fusiform) excision, (2) punch excision around the clinical lesion, or (3)

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deep shave/saucerization to a depth below the anticipated plane of the lesion, usually extending to the deep
reticular dermis.

Partial/incomplete sampling (incisional biopsy) is acceptable for lesions whose large size or location in a
challenging anatomic site (eg, facial, acral) precludes excisional biopsy, and for lesions with low clinical
suspicion or uncertainty of diagnosis. Such biopsies should include the most clinically and/or dermoscopically
atypical portion(s) of the lesion

Narrow-margin excisional biopsy may be performed if an initial partial biopsy is inadequate for diagnosis or
microstaging, but it should not generally be performed if the initial specimen meets the criteria for consideration
of sentinel lymph node biopsy.

Dermoscopy can improve diagnostic accuracy in lesions of clinical concern; it may help direct optimal and
adequate tissue sampling of very large lesions or those in cosmetically or functionally sensitive areas.

Prebiopsy photographs are an important aid to clinical/pathologic correlation and help to prevent wrong-site
surgery if further treatment is required. Photographs may be taken by the patient and/or health care provider and
should include a regional photograph that encompasses anatomic landmarks.

Findings from history and physical examination should direct need for further studies to detect local, regional,
and distant metastasis

Ancillary diagnostic molecular techniques (eg, comparative genomic hybridization; fluorescence in situ
hybridization, gene expression profiling [GEP]) may be used for equivocal melanocytic neoplasms, but routine
molecular testing, including GEP, for prognostication is discouraged until better use criteria are defined. Testing
of the primary cutaneous melanoma for oncogenic mutations (eg, BRAF, NRAS) is not recommended in the
absence of metastatic disease.

The 2015 guidelines from the European Society of Medical Oncology (ESMO) require diagnosis based on a full-
thickness excisional biopsy with a minimal side margin that has been processed by an experienced pathology
institute. Histology reports should include the following [88] :

Information on the type of melanoma

Actinic damage
Maximum vertical thickness in millimetres
Information on mitotic rate in case of pT1
Presence of ulceration
Presence and extent of regression
Clearance of the surgical margins

Physical examination with special attention to other suspicious pigmented lesions, tumour satellites, in-transit
metastases, regional LN and distant metastases is requried. Imaging is not needed for low-risk melanomas but is
required in higher tumor stages for accurate staging. [88]

The National Comprehensive Cancer Network (NCCN) supports the concept that most melanoma recurrences are
diagnosed clinically. Current NCCN guidelines state that no further workup (ie, baseline laboratory tests and imaging
studies) is required in stage 0 (melanoma in situ) and for asymptomatic patients with stage IA, IB, or IIA
melanoma. (Physician Quality Reporting System [PQRS] measure #224 concerns overutilization of imaging studies in
melanoma.)

Current NCCN guidelines do not recommend surveillance (follow-up) laboratory or imaging studies for asymptomatic
patients with stage IA, IB, and IIA melanoma (ie, tumors ≤4 mm depth). Imaging studies (chest radiograph, CT and/or
PET-CT) should be obtained as clinically indicated for confirmation of suspected metastasis or to delineate the extent
of disease. [21]

The NCCN advises that imaging studies may be considered to screen for recurrent/metastatic disease in patients with
stage IIB-IV disease, although this recommendation remains controversial. Routine laboratory or radiologic imaging

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in asymptomatic melanoma patients of any stage is not recommended after 5 years of follow-up. [21]

While abnormal laboratory test results are rarely the sole indicator of metastatic disease, serum lactate dehydrogenase
(LDH) levels are incorporated into the American Joint Committee on Cancer (AJCC) melanoma staging guidelines
for the classification of stage IV (distant) disease. Elevated LDH levels are associated with worse survival in this
subgroup. [25]

Previous
Next: Clinical Presentation and Workup

Surgical Management
AAD recommendations for surgical management of primary cutaneous melanoma are as follows [87] :

Surgical excision with histologically negative margins is the recommended and first-line treatment for primary
cutaneous melanoma of any thickness, as well as for melanoma in situ.
Surgical margins should be based on tumor thickness.
Depth of excision is recommended to (but not including) the fascia.
Sentinel lymph node biopsy, when indicated, should be performed before wide excision of the primary tumor,
and in the same operative setting, whenever possible.
Mohs micrographic surgery or staged excision with paraffin-embedded permanent sections may be utilized for
melanoma in situ, lentigo maligna type, on the face, ears, or scalp for tissue-sparing excision and exhaustive
histologic assessment of peripheral margins.

Previous
Next: Clinical Presentation and Workup

Sentinel Lymph Node Dissection

The melanoma guidelines from the National Comprehensive Cancer Network (NCCN) do not recommend sentinel
lymph node biopsy for patients with in situ melanoma (stage 0). [21]

Evidence supporting routine sentinel lymph node biopsy for patients with thin melanomas (T1; Breslow thickness < 1
mm) is lacking and recommendations remain controversial. The NCCN does not recommend sentinel lymph node
biopsy for patients with lesions 0.75 mm or thinner. [2] ESMO recommends sentinel lymph node biopsy with lesions
>1 mm and/or ulceration for precise staging. In addition, sentinel lymph node biopsy should be discussed with patients
with a T1b tumor greater than 0.75 mm. [88]

The American Academy of Dermatology (AAD) recommends consideration of sentinel lymph node biopsy in patients
with lesions, including those less than 0.76 mm, with any of the following high-risk features [86, 87] :

Ulceration
Mitosis
Angiolymphatic invasion
Positive deep margin
Young patient age

However, data suggest that the presence of a single mitotic figure may not correlate well with sentinel node status in
thin lesions. [89] In addition, the presence of regression in thin lesions is associated with a lower risk of nodal
metastasis. [90]

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The 2018 update of joint guidelines from the American Society of Clinical Oncology (ASCO) and Society of Surgical
Oncology (SSO) includes the following recommendations [27] :

Routine sentinel lymph node biopsy is not recommended for patients with thin melanomas that are T1a (non-
ulcerated lesions < 0.8 mm in Breslow thickness).
Sentinel lymph node biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow
thickness or < 0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the
potential benefits and risk of harms associated with the procedure.
Sentinel lymph node biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3;
Breslow thickness of >1.0 to 4.0 mm).
Sentinel lymph node biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow
thickness), after a discussion of the potential benefits and risks of harm.

In the case of a positive sentinel lymph node biopsy, completion lymph node dissection (CLND) or careful
observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathologic
factors. For higher-risk patients, careful observation may be considered only after a thorough discussion with patients
about the potential risks and benefits of foregoing CLND. [27]

Previous
Next: Clinical Presentation and Workup

Mohs Surgery
The NCCN cites a study of Mohs micrographic surgery (MMS) that employed MMS enhanced by
immunohistochemical staining as the primary treatment modality for melanoma in situ, which resulted in 99%
removal of melanoma in situ when a total surgical margin of 9 mm was used, versus an 86% rate of removal with 6-
mm margins. The stain comprised antibodies to a melanoma antigen recognized by T cells (MART-1). [21, 91]

The appropriate-use criteria for MMS from the AAD, American College of Mohs Surgery (ACMS), American Society
for Dermatologic Surgery Association (ASDSA), and the American Society for Mohs Surgery (ASMS) further state
that MMS is appropriate for all recurrent melanoma in situ and lentigo maligna, as well as primary lesions at the
following sites [92] :

Head
Neck
Hands
Feet
Pretibial surface
Nails
Ankles

For melanoma in situ, lentigo maligna type type, the AAD recommends permanent section analysis of the central
MMS debulking specimen to identify and appropriately stage potential invasive cutaneous melanoma. If invasive
cutaneous melanoma is identified on an MMS section intraoperatively, the tissue should be submitted for formal
pathology review. [87]

Previous
Next: Clinical Presentation and Workup
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Wide Excision Surgical Margins

For wide excision of primary melanoma, the NCCN, AAD and ESMO practice guidelines agree on the following
surgical margin recommendations for primary melanoma [21] 9884:

Tumor in situ – Margin size 0.5-1.0 cm

Tumor ≤ 1 mm – Margin size 1 cm

Tumor > 1 to 2 mm – Margin size 1-2 cm

Tumor > 2 mm – Margin size 2 cm

The AAD guidelines note that margins may be narrower to accommodate function and/or anatomic location.However,
for primary invasive melanomas at anatomically constrained sites (eg, head and neck, acral), margins of < 1 cm (by
either wide excision or Mohs micrographic surgery) are generally not recommended until further studies are available.
[87]

Previous
Next: Clinical Presentation and Workup

Radiation Therapy
NCCN guidelines recommend consideration of radiation therapy in the following situations [21] :

Primary disease: As adjuvant treatment in selected patients with factors that include deep desmoplastic
melanoma with narrow margins, extensive neurotropism, or locally recurrent disease

Regional disease: As adjuvant treatment following resection of category 2B nodes and LDH < 1.5 times the
upper limit of normal, and extranodal tumor extension; as palliative treatment for unresectable disease

Metastatic disease: As either adjuvant or primary treatment for brain metastases

ESMO recommends considering stereotactic radiation of regional or single distant metastatic disease. [88]

Previous
Next: Clinical Presentation and Workup

Treatment for Advanced Melanoma

NCCN recommendations for treatment of melanoma stage IV disease with distant metastasis include the following [21]
:

Treatment depends on whether melanoma is limited (resectable) or disseminated (unresectable)

In limited disease, resection is recommended; alternatively, observation or systemic therapy may be chosen
Treatment for limited disease includes clinical trial enrollment or systemic therapy
For patients with unresectable disease without brain metastases, treatment includes systemic therapy; patients
with brain metastases require treatment of the central nervous disease

First-line immunotherapy regimens for systemic therapy (category 1), according to the NCCN guidelines, are as
follows [21] :

Anti–PD-1 monotherapy: Pembrolizumab or nivolumab

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Nivolumab/ipilimumab

If the tumor contains a BRAF V600 activating mutation, category 1 recommendations for first-line therapy are as
follows [21] :

Dabrafenib plus trametinib

Vemurafenib plus cobimetinib

Second-line or subsequent therapy recommendations are as follows [21] :

Anti PD-1 monotherapy: Pembrolizumab or nivolumab

Nivolumab/ipilimumab
Targeted therapy if a BRAF V600 activating mutation is present: Dabrafenib/trametinib or
vemurafenib/cobimetinib
Ipilimumab
High-dose interleukin-2 (IL-2)
Cytotoxic agents
Imatinib for tumors with activating mutations of KIT

Previous
Next: Clinical Presentation and Workup

Follow-up for Melanoma Cancer Survivors

Follow-up guidelines from the National Comprehensive Cancer Network are listed below. [21]

Follow-up for stage 0 in situ is as follows:

At least annual skin examination for life

Educate patient in monthly self-examination of skin

Follow-up for stage IA is as follows:

History and physical examination (H&P), with emphasis on lymph nodes and skin, every 3-12 mo for 5 y, then
annually as clinically indicated

At least annual skin examination for life

Educate patient in monthly self-examination of skin and lymph nodes

Follow-up for stage IB-IV (patients with no evidence of disease) is as follows:

H&P (with emphasis on nodes and skin) every 3-6 mo for 2 y, then every 3-12 mo for 2 y, then annually as
clinically indicated

Chest radiography, lactate dehydrogenase (LDH) level, and complete blood cell count (CBC) every 6-12 mo
(optional)

Routine imaging is not recommended for stage IB or IIA disease

Computed tomography (CT) scans to follow up for specific signs and symptoms

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Consider CT and/or PET scans to screen stage IIB and higher for recurrent/metastatic disease every 3 to 12
months

At least annual skin examination for life

Educate patient in monthly self-examination of skin and lymph nodes

Previous
Medication

References

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Media Gallery

A 1.5-cm melanoma with characteristic asymmetry, irregular borders, and color variation.
Malignant melanoma. Image courtesy of Hon Pak, MD.
Lentigo maligna melanoma, right lower cheek. The centrally located erythematous papule represents invasive
melanoma with surrounding macular lentigo maligna (melanoma in situ). Image courtesy of Susan M. Swetter,
MD.

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Contributor Information and Disclosures

Author

Winston W Tan, MD, FACP Associate Professor of Medicine, Mayo Medical School; Consultant and Person-in-
Charge of Genitourinary Oncology-Medical Oncology, Division of Hematology/Oncology, Department of Internal
Medicine, Mayo Clinic Jacksonville; Vice Chairman, Division of Hematology/Oncology Education, Chair, Cancer
Survivorship Program, Associate Chair, Department of Medicine Faculty Development, Mayo Clinic Florida; Vice
President, Florida Society of Clinical Oncology

Winston W Tan, MD, FACP is a member of the following medical societies: American College of Physicians,
American Society of Clinical Oncology, American Society of Hematology, Philippine Medical Association, Texas
Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference

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12/11/2019 Malignant Melanoma Guidelines: Guidelines Summary, Clinical Presentation and Workup, Surgical Management

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical
University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Philip Schulman, MD Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center

Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research,
American College of Physicians, American Society of Hematology, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Mohsin R Mir, MD Private Practice, Mohs Micrographic Surgery and Dermatologic Surgery, Kelsey-Seybold Clinic;
Assistant Professor, Baylor College of Medicine

Mohsin R Mir, MD is a member of the following medical societies: American Academy of Dermatology, American
College of Mohs Surgery, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Wesley Wu, MD Mohs Surgeon, Department of Dermatology, VA Puget Sound and University of Washington

Wesley Wu, MD is a member of the following medical societies: American Academy of Dermatology, American
Society for Dermatologic Surgery, Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

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Sections Malignant Melanoma

Overview
Practice Essentials
Background
Etiology
Epidemiology
Prognosis
Patient Education
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History
Physical Examination
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DDx
Workup
Approach Considerations
Histologic Findings
Complete Chemistry Panel
Lactate Dehydrogenase Assay
Chest Radiography
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CT Scanning
Positron Emission Tomography
Biopsy of a Suggestive Lesion
Surgical Excision or Reexcision After Biopsy
Elective Lymph Node Dissection
Sentinel Lymph Node Biopsy
Staging
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Treatment
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Treatment of Advanced-Stage Melanoma (Stage IV)
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12/11/2019 Malignant Melanoma Guidelines: Guidelines Summary, Clinical Presentation and Workup, Surgical Management

Sentinel Lymph Node Dissection

Mohs Surgery
Wide Excision Surgical Margins
Radiation Therapy
Treatment for Advanced Melanoma
Follow-up for Melanoma Cancer Survivors
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